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Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens, including viruses, bacteria, and fungi, have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections are still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immunoregulatory roles during infection will also be discussed. [ABSTRACT FROM AUTHOR]

The Serous acini of airway submucosal glands are important for fluid secretion in the lung. Serous cells are also sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. However, the mechanisms of serous cell fluid secretion remain poorly defined. In this study, serous acinar cells were isolated from porcine bronchi and studied using optical techniques previously used to examine fluid secretion in rat parotid and murine nasal acinar cells. When stimulated with the cholinergic agonist carbachol, porcine serous cells shrank by -20% (observed via DIC microscopy) after a profound elevation of intracellular [Ca2+] ([Ca2+]i; measured by simultaneous fura 2 fluorescence imaging). Upon removal of agonist and relaxation of [Ca2+]i to resting levels, cells swelled back to resting volume. Similar results were observed during stimulation with histamine and ATP, and elevation of [Ca2+]i was found to be necessary and sufficient to activate shrinkage. Cell volume changes were associated with changes in [Cl-]i (measured using SPQ fluo- rescence), suggesting that shrinkage and swelling are caused by loss and gain of intracellular solute content, respectively, likely reflecting changes in the secretory state of the cells. Shrinkage was inhibited by niflumic acid but not by GIyH-101, suggesting Ca2+-activated secretion is mediated by alternative non-CFTR Cl- channels, possibly including Anol (TMEM16A), expressed on the apical membrane of porcine serous cells. Optimal cell swelling/solute uptake required activity of the Na+K+2Cl- cotransporter and Na+/H+ exchanger, both of which are expressed on the basolateral membrane of serous acini and likely contribute to sustaining transepithelial secretion. [ABSTRACT FROM AUTHOR]

Airway submucosal gland serous cells are important sites of fluid secretion in conducting airways. Serous cells also express the cystic fibrosis (CF) transmembrane conductance regulator (CFTR). Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor that activates secretion from intact airway glands. We tested if and how human nasal serous cells secrete fluid in response to PAR-2 stimulation using Ca2+ imaging and simultaneous differential interference contrast imaging to track isosmotic cell shrinking and swelling reflecting activation of solute efflux and influx pathways, respectively. During stimulation of PAR-2, serous cells exhibited dose-dependent increases in intracellular Ca2+. At stimulation levels >EC50 for Ca2+, serous cells simultaneously shrank 20% over 90s due to KCl efflux reflecting Ca2+-activated Cl- channel (CaCC, likely TMEM16A)-dependent secretion. At lower levels of PAR-2 stimulation (

The innate immune functions of human airways include mucociliary clearance and antimicrobial peptide activity. Both functions may be affected by changes in epithelial ion transport. Interleukin-17A (IL-17A), which has a receptor at the basolateral membrane of airway epithelia, is a T cell cytokine that has been shown to increase mucus secretion and antimicrobial peptide production by human bronchial epithelial (HBE) cells. Furthermore, IL-17A levels are increased in sputum from patients during pulmonary exacerbations of cystic fibrosis. Therefore, we investigated the effects of IL-17A on basal, amiloride-sensitive, and forskolin-stimulated ion transport in mature, well- differentiated HBE cells. Exposure of HBE monolayers to IL-17A for 48 h induced a novel forskolin-stimulated bicarbonate secretion in addition to forskolin-stimulated chloride secretion and resulted in alkalinization of liquid on the mucosal surface of polarized cells. IL-17A-induced bicarbonate secretion was cystic fibrosis transmembrane conductance regulator (CFTR)-dependent, mucosal chloride- dependent, partially Na+-dependent, and sensitive to serosal, but not mucosal, stilbene inhibition. These data suggest that IL-17A modulates epithelial bicarbonate secretion and implicate a mechanism by which airway surface liquid pH changes may be abnormal in cystic fibrosis. [ABSTRACT FROM AUTHOR]